Evidence has been presented which suggest that excitation-contraction coupling is altered in hypertrophied cardiac muscle. For instance, the compensation in hypertrophied rabbit heart muscle involves an increase in time to peak tension (Hamrell and Alpert, l977) which most likely reflects an alteration in the electrical activity of these muscles. Second, the decreased activation heat of hypertrophied muscle indicates an alteration in the excitation-contraction coupling system which may be mediated via an alteration in the eclectrophysiological behavior of the hypertrophied myocardium (Alpert and Mulieri, l977). Only limited information is available concerning correlated studies of the electrophysiological and mechanical properties of hypertrophied myocardium. In view of the critical role of the action potential and underlying ionic currents (especially the slow inward current) in the development of tension in cardiac muscle, a correlated study of the alteration in electrophysiological and mechanical properties of hypertrophied cardiac muscle should be undertaken. Consequently, the primary objective of the research program outlined in this proposal is to study the properties of the action potential, slow inward current, and mechanical performance in normal and hypertrophied myocardium. We suggest that the alteration in excitation-contraction coupling seen in hypertrophied myocardium may reflect an alteration in the slow inward (calcium) current system in this tissue. We plan to test this hypothesis with two separate, but closely coordinated, studies progressing in parallel. In the first, conventional microelectrode techniques will be utilized to investigate the basic electrical responses of normal and hypertrophied myocardium. Second, we will develop voltage clamp techniques to compare the voltage-tension relationship and slow inward current in preparations from normal and hypertrophied myocardium.